Yelenskiy Aleksandr, Ko MinHee K, Chu Edward R, Gonzalez Jose M, Siegmund Kimberly, Tan James C
Doheny Eye Institute and Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA, USA.
Tulane University Department of Ophthalmology, Tulane University School of Medicine, Tulane University, New Orleans, LA, USA.
Biomed Hub. 2017 Nov 17;2(3):1-10. doi: 10.1159/000484126. eCollection 2017 Sep-Dec.
To characterize total outflow facility across the live adult mouse lifespan as a reference for mouse glaucoma studies and the common C57BL/6 background strain.
Microperfusion was performed by single-needle cannulation and feedback-controlled coupling of pressure and flow to maintain a constant pressure in the anterior chambers of live C57BL/6NCrl mice aged 3-4 months ( = 17), 6-9 months ( = 10), and 23-27 months ( = 12). This mouse age range represented an equivalent human age range of young adult to elderly. We characterized the following across age groups in vivo: (1) outflow facility based on constant pressure perfusion in a pressure range of 15-35 mm Hg, (2) perfusion flow rates, and (3) anterior segment tissue histology after perfusion. Thirty-nine live mice underwent perfusion.
Pressure-flow rate functions were consistently linear for all age groups (all > 0.96). Total outflow facility in mice aged 3-4, 6-9, and 23-27 months was 0.0066, 0.0064, and 0.0077 μL/min/mm Hg, respectively. Facility was not significantly different between age groups (all > 0.4). The groups had closely overlapping frequency distribution profiles with right-sided tails. Post hoc estimates indicated that group facility differences of at least 50% would have been detectable, with this limit set mainly by inherent variability in the strain. A trend toward higher perfusion flow rates was seen in older mice aged 23-27 months, but this was not significantly different from that of mice aged 3-4 months or 6-9 months ( > 0.2). No histological disruption or difference in iridocorneal angle or drainage tissue structure was seen following perfusion in the different age groups.
We did not find a significant difference in total outflow facility between different age groups across the live C57BL/6 mouse adult lifespan, agreeing with some human studies. The possibility that more subtle differences might exist ought to be judged with respect to the heterogeneity in facility at different ages. Our findings provide reference data for live perfusion studies pertaining to glaucoma involving the C57BL/6 strain.
描述成年活体小鼠整个生命周期中的总房水流出易度,为小鼠青光眼研究及常见的C57BL/6背景品系提供参考。
通过单针插管及压力与流量的反馈控制耦合进行微灌注,以维持3至4个月龄(n = 17)、6至9个月龄(n = 10)和23至27个月龄(n = 12)的活体C57BL/6NCrl小鼠前房内的压力恒定。该小鼠年龄范围代表了从青年到老年的等效人类年龄范围。我们在体内对各年龄组进行了以下特征描述:(1)基于15至35 mmHg压力范围内的恒压灌注的流出易度,(2)灌注流速,以及(3)灌注后的眼前节组织组织学。39只活体小鼠接受了灌注。
所有年龄组的压力-流速函数均呈一致的线性(所有R²> 0.96)。3至4个月龄、6至9个月龄和23至27个月龄小鼠的总房水流出易度分别为0.0066、0.0064和0.0077 μL/min/mm Hg。各年龄组之间的流出易度无显著差异(所有P> 0.4)。这些组的频率分布曲线紧密重叠,尾部向右。事后估计表明,至少50%的组间流出易度差异是可检测到的,该限度主要由品系的固有变异性决定。在23至27个月龄的老年小鼠中观察到灌注流速有升高趋势,但这与3至4个月龄或6至9个月龄小鼠的流速无显著差异(P> 0.2)。在不同年龄组的灌注后,未观察到虹膜角膜角或引流组织结构的组织学破坏或差异。
我们未发现不同年龄组的活体C57BL/6小鼠成年生命周期中的总房水流出易度有显著差异,这与一些人体研究结果一致。关于不同年龄流出易度的异质性,应判断是否可能存在更细微的差异。我们的研究结果为涉及C57BL/6品系的青光眼活体灌注研究提供了参考数据。